Clinical Features and Diagnostic Challenges of Talaromyces marneffei Infection in Non-Endemic Regions: A 6-Case Study Highlighting NGS and Tailored Antifungal Therapy

Background: Talaromyces marneffei is an opportunistic fungal infection with marked geographical endemicity. While traditionally associated with HIV infection, its incidence is increasing in non-endemic areas, driven by improved diagnostics and a growing population of immunocompromised hosts. Methods: This retrospective study analyzed six cases (5 male, 1 female) of Talaromyces marneffei infection managed at Shaoxing People’s Hospital between 2023 and 2024, focusing on clinical manifestations, diagnostic approaches, and therapeutic outcomes. Results: Among the six patients (median age 44.5 years, range 24– 69 years), four were HIV-negative and two were HIV-positive. Non-HIV patients (4/6) presented with fever (4/4), productive cough (3/4), and lymphadenopathy (3/4), with underlying conditions including diabetes, autoimmune disorders, and myelofibrosis. Laboratory findings included lymphocytopenia, elevated CRP/ESR, and hypoalbuminemia. Imaging showed pulmonary infiltrates (3/4), hilar/mediastinal lymphadenopathy (3/4), and abscess (1/4). HIV-positive patients exhibited anemia, abdominal pain, disseminated lymphadenopathy, and splenomegaly, with reduced CD4 + T-cell percentages and elevated IgG. Due to atypical presentations, four cases were initially misdiagnosed. Diagnosis was confirmed via NGS (4/6), NGS plus culture (1/6), or histopathology (1/6). Treatment was individualized: severe cases received extended amphotericin B lipid complex (ABLC) (cumulative dose up to 31.8g in case1) induction followed by azole maintenance; milder cases received oral itraconazole alone. Two patients continue maintenance therapy; four discontinued after improvement with no relapse. All patients improved, and there were no deaths. Conclusion: This series highlights the diagnostic challenges of Talaromyces marneffei infection in non-endemic areas, especially among non-HIV immunocompromised hosts. NGS was essential for early detection. Individualized antifungal therapy-tailored to immune status and disease severity achieved favorable outcomes, underscoring the importance of personalized treatment strategies. Keywords: Talaromyces marneffei , diagnosis and treatment, NGS, amphotericin B lipid complex